Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus
Objective B cells with immunoregulatory properties (Breg cells) have been described in mice, but their role in the control of human immune responses is not well defined. We recently identified a human population of activated FSChigh B cells that exhibited regulatory activity toward T helper cells. T...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 June 2014
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| In: |
Arthritis & rheumatology
Year: 2014, Volume: 66, Issue: 10, Pages: 2849-2861 |
| ISSN: | 2326-5205 |
| DOI: | 10.1002/art.38742 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/art.38742 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/art.38742 
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| Author Notes: | Nele Gao, Julia Dresel, Volker Eckstein, Rimma Gellert, Hannah Störch, Ram K. C. Venigalla, Vedat Schwenger, Regina Max, Norbert Blank, Hanns-Martin Lorenz, and Theresa Tretter |
| Summary: | Objective B cells with immunoregulatory properties (Breg cells) have been described in mice, but their role in the control of human immune responses is not well defined. We recently identified a human population of activated FSChigh B cells that exhibited regulatory activity toward T helper cells. The aim of the present study was to test such induced Breg (iBreg) cells in patients with autoimmune disease. Methods Purified CD19+FSChigh B cells derived from patients with systemic lupus erythematosus (SLE) or from healthy donors, which were activated via their B cell receptor, were cocultured with CD3-stimulated CD4+ T helper cells from SLE patients or healthy donors. 3H-thymidine incorporation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to analyze proliferation, cytokine secretion, and surface marker expression. Results Although under costimulatory conditions, FSChigh SLE B cells supported the proliferation of healthy donor T cells to a similar extent as donor B cells, their regulatory function was significantly diminished in B cell suppressor assays. Similar effects were seen when SLE T cells were used, confirming that SLE T cells were equally susceptible to iBreg cell signals as healthy donor T cells and that SLE iBreg cell defects were independent of T cell origin. B cell viability and expression of surface markers (CD25, CD80, and B7-H1) or cytokines (interleukin-6 [IL-6], tumor necrosis factor α, and IL-10) were comparable in the two B cell populations. There was no correlation between the extent of iBreg cell-induced inhibition and disease activity. CD19+FSChigh B cells from patients with another systemic autoimmune disease, granulomatosis with polyangiitis (Wegener's) (GPA), exhibited no regulatory defects, which suggests that the iBreg cell defects were SLE-specific and not a general consequence of autoimmunity or inflammation. Conclusion Induced Breg cells from SLE patients, but not GPA patients, are less effective in the control of T helper cell proliferation, which supports the reported skewed B cell repertoire in SLE. The malfunctioning SLE iBreg cells might allow the overstimulation of immune responses and contribute to the initiation and/or perpetuation of disease. |
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| Item Description: | Gesehen am 21.07.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2326-5205 |
| DOI: | 10.1002/art.38742 |